The present invention relates to apoptosis-related antigenic compounds, such as fragments of cytokeratin 18, and antibodies or antigen-binding peptides recognizing said compounds, which are useful in medicaments, diagnostics and methods for the detection, monitoring, measurement and regulation of the type of cell death called programmed cell death or apoptosis. The determination of the occurrence of cell apoptosis may further be used for the monitoring of the effect of therapeutic treatment.
Apoptosis is seen in all sorts of higher eucaryocytes from plants and insects to vertebrates (Kroemer G, Petit P, Zanzami N, Vayssiere J -L, Mignotte B: The biochemistry of programmed cell death. The FASEB Journal 9:1277-1287 (1995)). Apoptosis is a general phenomenon of vital importance. Decreased apoptosis leads to malformation, cancer and autoimmune disease, and enhanced apoptosis results in degenerative diseases, acute diseases such as infection by toxin-producing microorganisms and in rejection of transplanted organs.
Therefore, the detection, monitoring, measurement and regulation of apoptosis are important factors in the diagnosis and therapeutic treatment of the mentioned conditions.
Recently, Caulin C., et al (The Journal of Cell Biology, Vol 138, pp. 1379-1394) studied caspase cleavage of Keratin 18 and reorganization of intermediate filaments during epitelial cell apoptosis. Keratin 18 was cleaved in vitro by caspase-6, -3, and -7, and it was stated that the cleavage site common for the three caspases was the sequence VEVD/A (SEQ ID NO:22), located in the conserved L1-2 linker region of K18.